Structure and dynamics of nano-sized raft-like domains on the plasma membrane

Abstract

Cell membranes are constitutively composed of thousands of different lipidic species, whose specific organization leads to functional heterogeneities. In particular, sphingolipids, cholesterol and some proteins associate among them to form stable nanoscale domains involved in recognition, signaling, membrane trafficking, etc. Atomic-detail information in the nanometer/second scale is still elusive to experimental techniques. In this context, molecular simulations on membrane systems have provided useful insights contributing to bridge this gap. Here we present the results of a series of simulations of biomembranes representing non-raft and raft-like nano-sized domains in order to analyze the particular structural and dynamical properties of these domains. Our results indicate that the smallest (5 nm) raft domains are able to preserve their distinctive structural and dynamical features, such as an increased thickness, higher ordering, lower lateral diffusion, and specific lipid-ion interactions. The insertion of a transmembrane protein helix into non-raft, extended raft-like, and raft-like nanodomain environments result in markedly different protein orientations, highlighting the interplay between the lipid-lipid and lipid-protein interactions.

A mixed alchemical and equilibrium dynamics to simulate heterogeneous dense fluids: Illustrations for Lennard-Jones mixtures and phospholipid membranes

“…Indeed, a large body of recent investigations has focused on model membranes with two or more components. [16][17][18][19][20][21] A study using a coarse-grained model of more than 60 different types of lipids represents to our knowledge the most diverse mixture studied with MD, 22 and a recent simulation using the Anton ASIC machine illustrated the capacity of straightforward MD to sample the equilibrium of a small two-component system from a phase separated state to a mixed state. 23 Nevertheless, significant challenges in simulation of heterogeneous membranes remain.…”

Lipid Raft Size and Lipid Mobility in Non-raft Domains Increase during Aging and Are Exacerbated in APP/PS1 Mice Model of Alzheimer's Disease. Predictions from an Agent-Based Mathematical Model

“…In this regard the mathematical approach represents a valid and potentially useful alternative to the study of the physicochemical properties and dynamic behavior of lipid rafts and their relation with its composition under normal and pathological conditions. In recent years, several studies have been published using in silico approaches (Nicolau et al, 2006 , 2007 ; Burrage et al, 2007 ; Richardson et al, 2007 ; Zhang et al, 2008 ; Herrera and Pantano, 2012 ; Soula et al, 2012 ). In some of these contributions, coarse grain models of cell membranes and lipid rafts have been reported (Marrink et al, 2008 ; Risselada and Marrink, 2008 ; Perlmutter and Sachs, 2009 , 2011 ; Kucerka et al, 2010 ; Schäfer and Marrink, 2010 ; de Joannis et al, 2011 ; Risselada et al, 2011 ; Rosetti and Pastorino, 2011 , 2012 ; Baoukina et al, 2012 ; Fischer et al, 2012 ; Muddana et al, 2012 ; Bennett and Tieleman, 2013 ; Davis et al, 2013 ; Hakobyan and Heuer, 2013 ; Marrink and Tieleman, 2013 ; Barnoud et al, 2014 ).…”

Signals in motion: Determining how signal transduction is mechanically coupled through type-I cytokine receptors

“…Indeed, changes in the tilt angle of a transmembrane domain as well as changes in the NMR structure between pure lipid and raft-like bilayers have been reported for other membrane receptors [93,94]. The simulations presented here support the studies that suggest the membrane composition heavily influences the structure and behaviour of proteins embedded in the membrane.…”